This application is for a five-year competing renewal of the University of Washington (UW) Superfund Basic Research Program Project. The theme of this Program Project is that biomarkers measured in accessible tissues are predictive of: a) toxicant exposures; b) early indicators of damage; and/or c) unusual susceptibility to toxic agents that commonly occur at hazardous waste sites. The proposed UW Program includes 5 research projects (biomedical and ecological/bioremediation), an Administrative Core, a Research Translation Core, a Functional Genomics and Bioinformatics Core, and an Outreach Core. The Program will focus most intensively on biomarker applications for investigations of adverse effects to human health and the environment from neurotoxic chemicals, primarily metals and pesticides. Collectively, these projects will develop and validate biomarkers for elucidating underlying neurotoxicity mechanisms, characterizing risks to humans, animals, and the environment, identifying host susceptibility traits that modify exposure/risk relations, and for implementing phytoremediation techniques. The research projects include studies of: 1) investigations of genetically-determined susceptibility factors predictive of mercury-related neurobehavioral impairment in children and adults; 2) animal models of susceptibility to organophosphate pesticides, with applications to human Parkinson's disease (PD); 3) environmental and genetic determinants of Parkinson's disease; 4) sub-lethal neurotoxic effects of metals and pesticides in free-living Coho salmon; 5) phytoremediation methods for organic solvents and pesticides. The Functional Genomics and Bioinformatics Core will provide extensive molecular biology laboratory and data analysis support to all research projects. Multidisciplinary collaborations among scientists specializing in neurotoxicology, epidemiology, molecular genetics, and bioinformatics will be emphasized as an essential feature of this highly integrated research program. The Administrative Core, directed by the Program Director, will oversee all major budgetary and personnel aspects of the Program Project, and will coordinate multidisciplinary interactions among research projects and cores. An External Science Advisory Board, composed of scientists from academia and government agencies, and an Internal Executive Committee that includes the Program Director, the Deputy Director, and selected program investigators, will provide scientific advice and oversight. The Research Translation Core will be responsible for communicating our research findings to community, government, and private sector stakeholders. This Core will also supervise technology transfer activities. The Outreach Core will coordinate efforts with the Research Translation Core to ensure appropriately tailored dissemination of research findings to community groups, government agencies, health professionals, and the broader scientific community.